Mechanisms of acute respiratory distress syndrome in children and adults: A review and suggestions for future research

Pediatric Critical Care Medicine

Volumn 14, Issue 6, 2013, Pages 631-643

  Smith, Lincoln S ^a   Zimmerman, Jerry J ^a   Martin, Thomas R ^b  

^a UNIVERSITY OF WASHINGTON   (United States)

^b NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Acute lung injury; Acute respiratory distress syndrome; Children; Lung inflammation; Lung repair; Mechanical ventilation

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1BETA; LUNG SURFACTANT;

ADULT RESPIRATORY DISTRESS SYNDROME; ALVEOLAR FLUID CLEARANCE; ALVEOLAR FLUID TRANSPORT; APOPTOSIS; BLOOD CLOTTING; CHILDHOOD DISEASE; DIRECT ALVEOLAR EPITHELIAL INJURY; FLUID TRANSPORT; GENE EXPRESSION; HUMAN; INNATE IMMUNITY; LUNG DEVELOPMENT; LUNG INJURY; MEDICAL LITERATURE; MEDICAL RESEARCH; MORTALITY; NONHUMAN; PATHOPHYSIOLOGY; POSTNATAL DEVELOPMENT; PRIORITY JOURNAL; PROTEIN EXPRESSION; RESPIRATORY TRACT PARAMETERS; REVIEW; SEPSIS; TRANSLATIONAL RESEARCH; VENTILATOR ASSOCIATED LUNG INJURY; VENTILATOR INDUCED LUNG INJURY;

EID: 84880804395     PISSN: 15297535     EISSN: 19473893     Source Type: Journal    
DOI: 10.1097/PCC.0b013e318291753f     Document Type: Review

References (188)

1. Burri PH, West JB, Crystal RG, et al: Postnatal development and growth. In: The Lung: Scientific Foundations. Crystal RG, West JB, Weibel ER, et al (Eds). Philadelphia, Lippincott-Raven Publishers, 1997, pp 1013-1026
2. Bernard GR, Artigas A, Brigham KL, et al: The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994; 149(3, Part 1): 818-824
3. ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, et al: Acute respiratory distress syndrome: The Berlin Definition. JAMA 2012; 307: 2526-2533
4. Thomas NJ, Jouvet P, Willson DF: Acute Lung Injury in Children - Kids Really Aren't Just 'Little Adults'. Pediatr Crit Care Med 2013; 14: 429-432
5. Bersten AD, Edibam C, Hunt T, et al; Australian and New Zealand Intensive Care Society Clinical Trials Group: Prevalence and mortality of acute lung injury and the acute respiratory distress syndrome in three Australian States. Am J Respir Crit Care Med 2002; 165: 443-448
6. Li G, Malinchoc M, Cartin-Ceba R, et al: Eight-year trend of acute respiratory distress syndrome: A population-based study in Olmsted County, Minnesota. Am J Respir Crit Care Med 2011; 183: 59-66
7. Luhr OR, Antonsen K, Karlsson M, et al: Prevalence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and Iceland. The ARF Study Group. Am J Respir Crit Care Med 1999; 159: 1849-1861
8. Rubenfeld GD, Caldwell E, Peabody E, et al: Prevalence and outcomes of acute lung injury. N Engl J Med 2005; 353: 1685-1693
9. Kneyber MC, Brouwers AG, Caris JA, et al: Acute respiratory distress syndrome: Is it underrecognized in the pediatric intensive care unit? Intensive Care Med 2008; 34: 751-754
10. Erickson SF, Schibler AF, Numa AF, et al: Acute lung injury in pediatric intensive care in Australia and New Zealand - A prospective, multicenter, observational study. Pediatr Crit Care Med 2007; 8: 317-323
11. Bindl L, Dresbach K, Lentze MJ: Prevalence of acute respiratory distress syndrome in German children and adolescents: A populationbased study. Crit Care Med 2005; 33: 209-312
12. Zimmerman JJ, Akhtar SR, Caldwell E, et al: Prevalence and outcomes of pediatric acute lung injury. Pediatrics 2009; 124: 87-95
13. Brun-Buisson C, Minelli C, Bertolini G, et al; ALIVE Study Group: Epidemiology and outcome of acute lung injury in European intensive care units. Results from the ALIVE study. Intensive Care Med 2004; 30: 51-61
14. Flori HR, Glidden DV, Rutherford GW, et al: Pediatric acute lung injury: Prospective evaluation of risk factors associated with mortality. Am J Respir Crit Care Med 2005; 171: 995-1001
15. Li Y, Wang Q, Chen H, et al: Epidemiological features and risk factor analysis of children with acute lung injury. World J Pediatr 2012; 8: 43-46
16. Dahlem P, van Aalderen WM, Hamaker ME, et al: Prevalence and short-term outcome of acute lung injury in mechanically ventilated children. Eur Respir J 2003; 22: 980-985
17. López-Fernández Y, Azagra AM, de la Oliva P, et al; Pediatric Acute Lung Injury Epidemiology and Natural History (PED-ALIEN) Network: Pediatric Acute Lung Injury Epidemiology and Natural History study: Prevalence and outcome of the acute respiratory distress syndrome in children. Crit Care Med 2012; 40: 3238-3245
18. Khemani RG, Patel NR, Bart RD III, et al: Comparison of the pulse oximetric saturation/fraction of inspired oxygen ratio and the PaO2/fraction of inspired oxygen ratio in children. Chest 2009; 135: 662-668
19. Quartin AA, Campos MA, Maldonado DA, et al: Acute lung injury outside of the ICU: Prevalence in respiratory isolation on a general ward. Chest 2009; 135: 261-268
20. Ferguson ND, Frutos-Vivar F, Esteban A, et al: Clinical risk conditions for acute lung injury in the intensive care unit and hospital ward: A prospective observational study. Crit Care 2007; 11: R96
21. Bindl L, Buderus S, Dahlem P, et al; ESPNIC ARDS Database Group: Gender-based differences in children with sepsis and ARDS: The ESPNIC ARDS Database Group. Intensive Care Med 2003; 29: 1770-1773
22. Santschi M, Jouvet P, Leclerc F, et al PALIVE Investigators; Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI); European Society of Pediatric and Neonatal Intensive Care (ESPNIC): Acute lung injury in children: Therapeutic practice and feasibility of international clinical trials. Pediatr Crit Care Med 2010; 11: 681-689
23. Johnston CJ, Rubenfeld GD, Hudson LD: Effect of age on the development of ARDS in trauma patients. Chest 2003; 124: 653-659
24. Erickson SE, Shlipak MG, Martin GS, et al; National Institutes of Health National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network: Racial and ethnic disparities in mortality from acute lung injury. Crit Care Med 2009; 37: 1-6
25. Kangelaris KN, Sapru A, Calfee CS, et al; National Heart, Lung, and Blood Institute ARDS Network: The association between a Darc gene polymorphism and clinical outcomes in African American patients with acute lung injury. Chest 2012; 141: 1160-1169
26. Yu WL, Lu ZJ, Wang Y, et al; Collaborative Study Group of Pediatric Respiratory Failure: The epidemiology of acute respiratory distress syndrome in pediatric intensive care units in China. Intensive Care Med 2009; 35: 136-143
27. Hu X, Qian S, Xu F, et al; Chinese Collaborative Study Group for Pediatric Respiratory Failure: Prevalence, management and mortality of acute hypoxemic respiratory failure and acute respiratory distress syndrome from a prospective study of Chinese paediatric intensive care network. Acta Paediatr 2010; 99: 715-721
28. Agarwal R, Srinivas R, Nath A, et al: Is the mortality higher in the pulmonary vs the extrapulmonary ARDS? A meta analysis. Chest 2008; 133: 1463-1473
29. Sevransky JE, Martin GS, Mendez-Tellez P, et al: Pulmonary vs nonpulmonary sepsis and mortality in acute lung injury. Chest 2008; 134: 534-538
30. ATS: Mechanisms and limits of induced postnatal lung growth. Am J Respir Crit Care Med 2004; 170: 319-343
31. Warburton D, Schwarz M, Tefft D, et al: The molecular basis of lung morphogenesis. Mech Dev 2000; 92: 55-81
32. Whitsett JA, Wert SE, Chernick V, et al: Molecular determinants of lung development. In: Kendig's Disorders of the Respiratory Tract in Children. Chernick V, Boat TF (Eds). Philadelphia, W.B. Saunders Company, 1998, pp 3-19
33. Whitsett JA: Intrinsic and innate defenses in the lung: Intersection of pathways regulating lung morphogenesis, host defense, and repair. J Clin Invest 2002; 109: 565-569
34. Londhe VA, Nguyen HT, Jeng JM, et al: NF-κB induces lung maturation during mouse lung morphogenesis. Dev Dyn 2008; 237: 328-338
35. Muraoka RS, Bushdid PB, Brantley DM, et al: Mesenchymal expression of nuclear factor-kappaB inhibits epithelial growth and branching in the embryonic chick lung. Dev Biol 2000; 225: 322-338
36. Kramer BW, Kallapur S, Newnham J, et al: Prenatal inflammation and lung development. Semin Fetal Neonatal Med 2009; 14: 2-7
37. Hagberg H, Wennerholm UB, Sävman K: Sequelae of chorioamnionitis. Curr Opin Infect Dis 2002; 15: 301-306
38. Lecart C, Cayabyab R, Buckley S, et al: Bioactive transforming growth factor-beta in the lungs of extremely low birthweight neonates predicts the need for home oxygen supplementation. Biol Neonate 2000; 77: 217-223
39. Bartram U, Speer CP: The role of transforming growth factor beta in lung development and disease. Chest 2004; 125: 754-765
40. Fahy RJ, Lichtenberger F, McKeegan CB, et al: The acute respiratory distress syndrome: A role for transforming growth factor-beta 1. Am J Respir Cell Mol Biol 2003; 28: 499-503
41. de Pablo R, Monserrat J, Reyes E, et al: Sepsis-induced acute respiratory distress syndrome with fatal outcome is associated to increased serum transforming growth factor beta-1 levels. Eur J Intern Med 2012; 23: 358-362
42. Smith LS, Gharib SA, Frevert CW, et al: Effects of age on the synergistic interactions between lipopolysaccharide and mechanical ventilation in mice. Am J Respir Cell Mol Biol 2010; 43: 475-486
43. Lewis DB, Wilson CB: Developmental immunology and role of host defenses in fetal and neonatal susceptibility to infection. In: Infectious Diseases of the Fetus and Newborn Infant. Remington JS, Klein JO, Wilson CB (Eds). Philadelphia, Elsevier Saunders, 2006, pp 87-210
44. Flori HR, Ware LB, Glidden D, et al: Early elevation of plasma soluble intercellular adhesion molecule-1 in pediatric acute lung injury identifies patients at increased risk of death and prolonged mechanical ventilation. Pediatr Crit Care Med 2003; 4: 315-321
45. Calfee CS, Eisner MD, Parsons PE, et al: Soluble intercellular adhesion molecule-1 and clinical outcomes in patients with acute lung injury. Intensive Care Med 2009; 35: 248-257
46. Bortolussi R, Howlett S, Rajaraman K, et al: Deficient priming activity of newborn cord blood-derived polymorphonuclear neutrophilic granulocytes with lipopolysaccharide and tumor necrosis factor-alpha triggered with formyl-methionyl-leucyl-phenylalanine. Pediatr Res 1993; 34: 243-248
47. Lee SM, Suen Y, Chang L, et al: Decreased interleukin-12 (IL-12) from activated cord versus adult peripheral blood mononuclear cells and upregulation of interferon-gamma, natural killer, and lymphokineactivated killer activity by IL-12 in cord blood mononuclear cells. Blood 1996; 88: 945-954
48. Peters AM, Bertram P, Gahr M, et al: Reduced secretion of interleukin- 1 and tumor necrosis factor-alpha by neonatal monocytes. Biol Neonate 1993; 63: 157-162
49. Qing G, Rajaraman K, Bortolussi R: Diminished priming of neonatal polymorphonuclear leukocytes by lipopolysaccharide is associated with reduced CD14 expression. Infect Immun 1995; 63: 248-252
50. Yan SR, Qing G, Byers DM, et al: Role of MyD88 in diminished tumor necrosis factor alpha production by newborn mononuclear cells in response to lipopolysaccharide. Infect Immun 2004; 72: 1223-1229
51. Baltimore D: NF-κB is 25. Nat Immunol 2011; 12: 683-685
52. Oeckinghaus A, Hayden MS, Ghosh S: Crosstalk in NF-[kappa] B signaling pathways. Nat Immunol 2011; 12: 695-708
53. Yang G, Abate A, George AG, et al: Maturational differences in lung NF-{kappa}B activation and their role in tolerance to hyperoxia. J Clin Invest 2004; 114: 669-678
54. Alvira CM, Abate A, Yang G, et al: Nuclear factor-kB activation in neonatal mouse lung protects against lipopolysaccharide-induced inflammation. Am J Respir Crit Care Med 2007; 175: 805-815
55. Patton LM, Saggart BS, Ahmed NK, et al: Interleukin-1 beta-induced neutrophil recruitment and acute lung injury in hamsters. Inflammation 1995; 19: 23-29
56. Pugin J, Ricou B, Steinberg KP, et al: Proinflammatory activity in bronchoalveolar lavage fluids from patients with ARDS, a prominent role for interleukin-1. Am J Respir Crit Care Med 1996; 153(6, Part 1): 1850-1856
57. Patwari PP, O'Cain P, Goodman DM, et al: Interleukin-1 receptor antagonist intron 2 variable number of tandem repeats polymorphism and respiratory failure in children with community-acquired pneumonia. Pediatr Crit Care Med 2008; 9: 553-559
58. Reiner AP, Wurfel MM, Lange LA, et al: Polymorphisms of the IL1- receptor antagonist gene (IL1RN) are associated with multiple markers of systemic inflammation. Arterioscler Thromb Vasc Biol 2008; 28: 1407-1412
59. Maniatis NA, Orfanos SE: The endothelium in acute lung injury/acute respiratory distress syndrome. Curr Opin Crit Care 2008; 14: 22-30
60. Gattinoni L, Pelosi P, Suter PM, et al: Acute respiratory distress syndrome caused by pulmonary and extrapulmonary disease. Different syndromes? Am J Respir Crit Care Med 1998; 158: 3-11
61. Matthay MA, Wiener-Kronish JP: Intact epithelial barrier function is critical for the resolution of alveolar edema in humans. Am Rev Respir Dis 1990; 142(6, Part 1): 1250-1257
62. Ware LB, Matthay MA: Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med 2001; 163: 1376-1383
63. Valentine SL, Sapru A, Higgerson RA, et al: Fluid balance in critically ill children with acute lung injury. Crit Care Med 2012; 40: 2883-2889
64. ARDSNet: Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006; 354: 2564-2575
65. Matthay MA, Folkesson HG, Clerici C: Lung epithelial fluid transport and the resolution of pulmonary edema. Physiol Rev 2002; 82: 569-600
66. Sweezey N, Tchepichev S, Gagnon S, et al: Female gender hormones regulate mRNA levels and function of the rat lung epithelial Na channel. Am J Physiol 1998; 274(2, Part 1): C379-C386
67. Henson PM, Tuder RM: Apoptosis in the lung: Induction, clearance and detection. Am J Physiol Lung Cell Mol Physiol 2008; 294: L601-L611
68. Perkins GD, McAuley DF, Thickett DR, et al: The beta-agonist lung injury trial (BALTI): A randomized placebo-controlled clinical trial. Am J Respir Crit Care Med 2006; 173: 281-287
69. Liu KD, Levitt J, Zhuo H, et al: Randomized clinical trial of activated protein C for the treatment of acute lung injury. Am J Respir Crit Care Med 2008; 178: 618-623
70. Ware LB, Matthay MA: Keratinocyte and hepatocyte growth factors in the lung: Roles in lung development, inflammation, and repair. Am J Physiol Lung Cell Mol Physiol 2002; 282: L924-L940
71. Griese M: Pulmonary surfactant in health and human lung diseases: State of the art. Eur Respir J 1999; 13: 1455-1476
72. McCormack FX, Whitsett JA: The pulmonary collectins, SP-A and SP-D, orchestrate innate immunity in the lung. J Clin Invest 2002; 109: 707-712
73. Lewis JF, Brackenbury A: Role of exogenous surfactant in acute lung injury. Crit Care Med 2003; 31(4 Suppl): S324-S328
74. Martin TR, Nakamura M, Matute-Bello G: The role of apoptosis in acute lung injury. Crit Care Med 2003; 31(4 Suppl): S184-S188
75. Dulkerian SJ, Gonzales LW, Ning Y, et al: Regulation of surfactant protein D in human fetal lung. Am J Respir Cell Mol Biol 1996; 15: 781-786
76. Zhu S, Ware LB, Geiser T, et al: Increased levels of nitrate and surfactant protein a nitration in the pulmonary edema fluid of patients with acute lung injury. Am J Respir Crit Care Med 2001; 163: 166-172
77. Greene KE, Wright JR, Steinberg KP, et al: Serial changes in surfactant- associated proteins in lung and serum before and after onset of ARDS. Am J Respir Crit Care Med 1999; 160: 1843-1850
78. Currier PF, Gong MN, Zhai R, et al: Surfactant protein-B polymorphisms and mortality in the acute respiratory distress syndrome. Crit Care Med 2008; 36: 2511-2516
79. Quasney MW, Waterer GW, Dahmer MK, et al: Association between surfactant protein B + 1580 polymorphism and the risk of respiratory failure in adults with community-acquired pneumonia. Crit Care Med 2004; 32: 1115-1119
80. Davidson WJ, Dorscheid D, Spragg R, et al: Exogenous pulmonary surfactant for the treatment of adult patients with acute respiratory distress syndrome: results of a meta-analysis. Crit Care 2006; 10: R41
81. Taut FJ, Rippin G, Schenk P, et al: A search for subgroups of patients with ARDS who may benefit from surfactant replacement therapy: A pooled analysis of five studies with recombinant surfactant protein-C surfactant (Venticute). Chest 2008; 134: 724-732
82. LeVine AM, Lotze A, Stanley S, et al: Surfactant content in children with inflammatory lung disease. Crit Care Med 1996; 24: 1062-1067
83. Dahmer MK, O'cain P, Patwari PP, et al: The influence of genetic variation in surfactant protein B on severe lung injury in African American children. Crit Care Med 2011; 39: 1138-1144
84. Duffett M, Choong K, Ng V, et al: Surfactant therapy for acute respiratory failure in children: A systematic review and meta-analysis. Crit Care 2007; 11: R66
85. Willson DF, Thomas NJ, Markovitz BP, et al: Effect of exogenous surfactant (calfactant) in pediatric acute lung injury: A randomized controlled trial. JAMA 2005; 293: 470-476
86. Matute-Bello G, Liles WC, Radella F II, et al: Modulation of neutrophil apoptosis by granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor during the course of acute respiratory distress syndrome. Crit Care Med 2000; 28: 1-7
87. Haslett C, Savill JS, Whyte MK, et al: Granulocyte apoptosis and the control of inflammation. Philos Trans R Soc Lond B Biol Sci 1994; 345: 327-333
88. Park WY, Goodman RB, Steinberg KP, et al: Cytokine balance in the lungs of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 2001; 164(10, Part 1): 1896-1903
89. Guinee D Jr, Brambilla E, Fleming M, et al: The potential role of BAX and BCL-2 expression in diffuse alveolar damage. Am J Pathol 1997; 151: 999-1007
90. Albertine KH, Soulier MF, Wang Z, et al: Fas and fas ligand are upregulated in pulmonary edema fluid and lung tissue of patients with acute lung injury and the acute respiratory distress syndrome. Am J Pathol 2002; 161: 1783-1796
91. Matute-Bello G, Liles WC, Steinberg KP, et al: Soluble Fas ligand induces epithelial cell apoptosis in humans with acute lung injury (ARDS). J Immunol 1999; 163: 2217-2225
92. Nicholson DW: From bench to clinic with apoptosis-based therapeutic agents. Nature 2000; 407: 810-816
93. Matute-Bello G, Liles WC, Frevert CW, et al: Blockade of the Fas/FasL system improves pneumococcal clearance from the lungs without preventing dissemination of bacteria to the spleen. J Infect Dis 2005; 191: 596-606
94. Hotchkiss RS, Swanson PE, Knudson CM, et al: Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis. J Immunol 1999; 162: 4148-4156
95. Ma Y, Liu H, Tu-Rapp H, et al: Fas ligation on macrophages enhances IL-1R1-Toll-like receptor 4 signaling and promotes chronic inflammation. Nat Immunol 2004; 5: 380-387
96. Zhande R, Dauphinee SM, Thomas JA, et al: FADD negatively regulates lipopolysaccharide signaling by impairing interleukin-1 receptor- associated kinase 1-MyD88 interaction. Mol Cell Biol 2007; 27: 7394-7404
97. Cory S, Adams JM: The Bcl2 family: Regulators of the cellular life-ordeath switch. Nat Rev Cancer 2002; 2: 647-656
98. Kuwano K, Hara N: Signal transduction pathways of apoptosis and inflammation induced by the tumor necrosis factor receptor family. Am J Respir Cell Mol Biol 2000; 22: 147-149
99. White MK, Baireddy V, Strayer DS: Natural protection from apoptosis by surfactant protein A in type II pneumocytes. Exp Cell Res 2001; 263: 183-192
100. Vázquez de Lara L, Becerril C, Montaño M, et al: Surfactant components modulate fibroblast apoptosis and type I collagen and collagenase- 1 expression. Am J Physiol Lung Cell Mol Physiol 2000; 279: L950-L957
101. Schagat TL, Wofford JA, Wright JR: Surfactant protein A enhances alveolar macrophage phagocytosis of apoptotic neutrophils. J Immunol 2001; 166: 2727-2733
102. Hagiwara S, Iwasaka H, Matumoto S, et al: Effects of an angiotensinconverting enzyme inhibitor on the inflammatory response in in vivo and in vitro models. Crit Care Med 2009; 37: 626-633
103. Lukkarinen HP, Laine J, Aho H, et al: Angiotensin II receptor inhibition prevents pneumocyte apoptosis in surfactant-depleted rat lungs. Pediatr Pulmonol 2005; 39: 349-358
104. Mantell LL, Horowitz S, Davis JM, et al: Hyperoxia-induced cell death in the lung - The correlation of apoptosis, necrosis, and inflammation. Ann N Y Acad Sci 1999; 887: 171-180
105. Herrero R, Kajikawa O, Matute-Bello G, et al: The biological activity of FasL in human and mouse lungs is determined by the structure of its stalk region. J Clin Invest 2011; 121: 1174-1190
106. Yamada T, Iwasaki Y, Nagata K, et al: Thioredoxin-1 protects against hyperoxia-induced apoptosis in cells of the alveolar walls. Pulm Pharmacol Ther 2007; 20: 650-659
107. Le A, Damico R, Damarla M, et al: Alveolar cell apoptosis is dependent on p38 MAP kinase-mediated activation of xanthine oxidoreductase in ventilator-induced lung injury. J Appl Physiol 2008; 105: 1282-1290
108. Schittny JC, Djonov V, Fine A, et al: Programmed cell death contributes to postnatal lung development. Am J Respir Cell Mol Biol 1998; 18: 786-793
109. Upadhyay D, Correa-Meyer E, Sznajder JI, et al: FGF-10 prevents mechanical stretch-induced alveolar epithelial cell DNA damage via MAPK activation. Am J Physiol Lung Cell Mol Physiol 2003; 284: L350-L359
110. Bao S, Wang Y, Sweeney P, et al: Keratinocyte growth factor induces Akt kinase activity and inhibits Fas-mediated apoptosis in A549 lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 2005; 288: L36-L42
111. Undevia NS, Dorscheid DR, Marroquin BA, et al: Smad and p38- MAPK signaling mediates apoptotic effects of transforming growth factor-{beta}1 in human airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 2004; 287: L515-L524
112. Bland R, Ertsey R, Mokres L, et al: Mechanical ventilation uncouples synthesis and assembly of elastin and increases apoptosis in lungs of newborn mice: Prelude to defective alveolar septation during lung development? Am J Physiol Lung Cell Mol Physiol 2007; 294: L3-L14
113. Flori HR, Ware LB, Milet M, et al: Early elevation of plasma von Willebrand factor antigen in pediatric acute lung injury is associated with an increased risk of death and prolonged mechanical ventilation. Pediatr Crit Care Med 2007; 8: 96-101
114. Ware LB, Fang X, Matthay MA: Protein C and thrombomodulin in human acute lung injury. Am J Physiol Lung Cell Mol Physiol 2003; 285: L514-L521
115. Ware LB, Fang X, Matthay MA: Protein C and thrombomodulin in human acute lung injury. Am J Physiol Lung Cell Mol Physiol 2003; 285: L514-L521
116. Ware LB, Eisner MD, Thompson BT, et al: Significance of von Willebrand factor in septic and nonseptic patients with acute lung injury. Am J Respir Crit Care Med 2004; 170: 766-772
117. Prabhakaran P, Ware LB, White KE, et al: Elevated levels of plasminogen activator inhibitor-1 in pulmonary edema fluid are associated with mortality in acute lung injury. Am J Physiol Lung Cell Mol Physiol 2003; 285: L20-L28
118. Sapru A, Curley MA, Brady S, et al: Elevated PAI-1 is associated with poor clinical outcomes in pediatric patients with acute lung injury. Intensive Care Med 2010; 36: 157-163
119. ARDSNet: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000; 342: 1301-1308
120. Parsons PE, Matthay MA, Ware LB, et al; National Heart, Lung, Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network: Elevated plasma levels of soluble TNF receptors are associated with morbidity and mortality in patients with acute lung injury. Am J Physiol Lung Cell Mol Physiol 2005; 288: L426-L431
121. Parsons PE, Eisner MD, Thompson BT, et al: Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Crit Care Med 2005; 33: 1-6
122. Tremblay LN, Slutsky AS: Ventilator-induced injury: From barotrauma to biotrauma. Proc Assoc Am Physicians 1998; 110: 482-488
123. Tremblay L, Valenza F, Ribeiro SP, et al: Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model. J Clin Invest 1997; 99: 944-952
124. Vlahakis NE, Hubmayr RD: Response of alveolar cells to mechanical stress. Curr Opin Crit Care 2003; 9: 2-8
125. Dreyfuss D, Saumon G: Ventilator-induced lung injury: Lessons from experimental studies. Am J Respir Crit Care Med 1998; 157: 294-323
126. Plötz FB, Vreugdenhil HA, Slutsky AS, et al: Mechanical ventilation alters the immune response in children without lung pathology. Intensive Care Med 2002; 28: 486-492
127. Copland I, Post M: Lung development and fetal lung growth. Paediatr Respir Rev 2004; 5 Suppl A: S259-S264
128. Kornecki A, Tsuchida S, Ondiveeran HK, et al: Lung development and susceptibility to ventilator-induced lung injury. Am J Respir Crit Care Med 2005; 171: 743-752
129. Chang L, Karin M: Mammalian MAP kinase signalling cascades. Nature 2001; 410: 37-40
130. Correa-Meyer E, Pesce L, Guerrero C, et al: Cyclic stretch activates ERK1/2 via G proteins and EGFR in alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol 2002; 282: L883-L891
131. Pugin J: Molecular mechanisms of lung cell activation induced by cyclic stretch. Crit Care Med 2003; 31(4 Suppl): S200-S206
132. Warburton D, Bellusci S: The molecular genetics of lung morphogenesis and injury repair. Paediatr Respir Rev 2004; 5 Suppl A: S283-S287
133. Colucci G, Domenighetti G, Della Bruna R, et al: Comparison of two non-bronchoscopic methods for evaluating inflammation in patients with acute hypoxaemic respiratory failure. Crit Care 2009; 13: R134
134. Carter SR, Davis CS, Kovacs EJ: Exhaled breath condensate collection in the mechanically ventilated patient. Respir Med 2012; 106: 601-613
135. Tremblay LN, Slutsky AS: Ventilator-induced lung injury: From the bench to the bedside. Intensive Care Med 2006; 32: 24-33
136. Dos Santos CC, Slutsky AS: Invited review: Mechanisms of ventilator- induced lung injury: A perspective. J Appl Physiol 2000; 89: 1645-1655
137. Matthay MA, Zimmerman GA, Esmon C, et al: Future research directions in acute lung injury: Summary of a National Heart, Lung, and Blood Institute working group. Am J Respir Crit Care Med 2003; 167: 1027-1035
138. Moriyama K, Ishizaka A, Nakamura M, et al: Enhancement of the endotoxin recognition pathway by ventilation with a large tidal volume in rabbits. Am J Physiol Lung Cell Mol Physiol 2004; 286: L1114-L1121
139. Brégeon F, Delpierre S, Chetaille B, et al: Mechanical ventilation affects lung function and cytokine production in an experimental model of endotoxemia. Anesthesiology 2005; 102: 331-339
140. Herrera MT, Toledo C, Valladares F, et al: Positive end-expiratory pressure modulates local and systemic inflammatory responses in a sepsis-induced lung injury model. Intensive Care Med 2003; 29: 1345-1353
141. Altemeier WA, Matute-Bello G, Frevert CW, et al: Mechanical ventilation with moderate tidal volumes synergistically increases lung cytokine response to systemic endotoxin. Am J Physiol Lung Cell Mol Physiol 2004; 287: L533-L542
142. Altemeier WA, Matute-Bello G, Gharib SA, et al: Modulation of lipopolysaccharide- induced gene transcription and promotion of lung injury by mechanical ventilation. J Immunol 2005; 175: 3369-3376
143. Dhanireddy S, Altemeier WA, Matute-Bello G, et al: Mechanical ventilation induces inflammation, lung injury, and extra-pulmonary organ dysfunction in experimental pneumonia. Lab Invest 2006; 86: 790-799
144. Embrace the complexity. Nat Immunol 2009; 10: 325
145. Adamson IY, Bakowska J: Relationship of keratinocyte growth factor and hepatocyte growth factor levels in rat lung lavage fluid to epithelial cell regeneration after bleomycin. Am J Pathol 1999; 155: 949-954
146. Pugin J, Verghese G, Widmer MC, et al: The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome. Crit Care Med 1999; 27: 304-312
147. Clark JG, Milberg JA, Steinberg KP, et al: Elevated lavage levels of N-terminal peptide of type III procollagen are associated with increased fatality in adult respiratory distress syndrome. Chest 1994; 105(3 Suppl): 126S-127S
148. Meduri GU: Late adult respiratory distress syndrome. New Horiz 1993; 1: 563-577
149. Clark JG, Milberg JA, Steinberg KP, et al: Type III procollagen peptide in the adult respiratory distress syndrome. Association of increased peptide levels in bronchoalveolar lavage fluid with increased risk for death. Ann Intern Med 1995; 122: 17-23
150. Snyder LS, Hertz MI, Harmon KR, et al: Failure of lung repair following acute lung injury. Regulation of the fibroproliferative response (Part 1). Chest 1990; 98: 733-738
151. Meduri GU, Headley S, Kohler G, et al: Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-1 beta and IL-6 levels are consistent and efficient predictors of outcome over time. Chest 1995; 107: 1062-1073
152. Bitterman PB: Pathogenesis of fibrosis in acute lung injury. Am J Med 1992; 92(6A): 39S-43S
153. Chesnutt AN, Matthay MA, Tibayan FA, et al: Early detection of type III procollagen peptide in acute lung injury. Pathogenetic and prognostic significance. Am J Respir Crit Care Med 1997; 156(3, Part 1): 840-845
154. Kolb M, Margetts PJ, Anthony DC, et al: Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis. J Clin Invest 2001; 107: 1529-1536
155. Geiser T, Atabai K, Jarreau PH, et al: Pulmonary edema fluid from patients with acute lung injury augments in vitro alveolar epithelial repair by an IL-1beta-dependent mechanism. Am J Respir Crit Care Med 2001; 163: 1384-1388
156. Geiser T, Jarreau PH, Atabai K, et al: Interleukin-1beta augments in vitro alveolar epithelial repair. Am J Physiol Lung Cell Mol Physiol 2000; 279: L1184-L1190
157. Olman MA, White KE, Ware LB, et al: Pulmonary edema fluid from patients with early lung injury stimulates fibroblast proliferation through IL-1 beta-induced IL-6 expression. J Immunol 2004; 172: 2668-2677
158. Lindroos PM, Coin PG, Osornio-Vargas AR, et al: Interleukin 1 beta (IL-1 beta) and the IL-1 beta-alpha 2-macroglobulin complex upregulate the platelet-derived growth factor alpha-receptor on rat pulmonary fibroblasts. Am J Respir Cell Mol Biol 1995; 13: 455-465
159. Pittet JF, Griffiths MJ, Geiser T, et al: TGF-beta is a critical mediator of acute lung injury. J Clin Invest 2001; 107: 1537-1544
160. Shull MM, Ormsby I, Kier AB, et al: Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 1992; 359: 693-699
161. Gauldie J, Sime PJ, Xing Z, et al: Transforming growth factor-beta gene transfer to the lung induces myofibroblast presence and pulmonary fibrosis. Curr Top Pathol 1999; 93: 35-45
162. Sime PJ, Marr RA, Gauldie D, et al: Transfer of tumor necrosis factoralpha to rat lung induces severe pulmonary inflammation and patchy interstitial fibrogenesis with induction of transforming growth factorbeta1 and myofibroblasts. Am J Pathol 1998; 153: 825-832
163. Zhou Y, Koli K, Hagood JS, et al: Latent transforming growth factor- beta-binding protein-4 regulates transforming growth factorbeta1 bioavailability for activation by fibrogenic lung fibroblasts in response to bleomycin. Am J Pathol 2009; 174: 21-33
164. Bonniaud P, Margetts PJ, Kolb M, et al: Progressive transforming growth factor beta1-induced lung fibrosis is blocked by an orally active ALK5 kinase inhibitor. Am J Respir Crit Care Med 2005; 171: 889-898
165. Klass BR, Grobbelaar AO, Rolfe KJ: Transforming growth factor beta1 signalling, wound healing and repair: A multifunctional cytokine with clinical implications for wound repair, a delicate balance. Postgrad Med J 2009; 85: 9-14
166. Meduri GU, Carratu P, Freire AX: Evidence of biological efficacy for prolonged glucocorticoid treatment in patients with unresolving ARDS. Eur Respir J Suppl 2003; 42: 57s-64s
167. Thompson BT: Glucocorticoids and acute lung injury. Crit Care Med 2003; 31(4 Suppl): S253-S257
168. Bernard GR, Luce JM, Sprung CL, et al: High-dose corticosteroids in patients with the adult respiratory distress syndrome. N Engl J Med 1987; 317: 1565-1570
169. Meduri GU, Golden E, Freire AX, et al: Methylprednisolone infusion in early severe ARDS: Results of a randomized controlled trial. Chest 2007; 131: 954-963
170. Steinberg KP, Hudson LD, Goodman RB, et al: Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 2006; 354: 1671-1684
171. Meduri GU, Headley AS, Golden E, et al: Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: A randomized controlled trial. JAMA 1998; 280: 159-165
172. Agarwal R, Nath A, Aggarwal AN, et al: Do glucocorticoids decrease mortality in acute respiratory distress syndrome? A meta-analysis. Respirology 2007; 12: 585-590
173. Meduri GU, Marik PE, Chrousos GP, et al: Steroid treatment in ARDS: A critical appraisal of the ARDS network trial and the recent literature. Intensive Care Med 2008; 34: 61-69
174. Tang BM, Craig JC, Eslick GD, et al: Use of corticosteroids in acute lung injury and acute respiratory distress syndrome: A systematic review and meta-analysis. Crit Care Med 2009; 37: 1594-1603
175. Peter JV, John P, Graham PL, et al: Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: Meta-analysis. BMJ 2008; 336: 1006-1009
176. Wilcox ME, Herridge MS: Long-term outcomes in patients surviving acute respiratory distress syndrome. Semin Respir Crit Care Med 2010; 31: 55-65
177. Narang I: Review series: What goes around, comes around: Childhood influences on later lung health? Long-term follow-up of infants with lung disease of prematurity. Chron Respir Dis 2010; 7: 259-269
178. Castro M, Ramirez MI, Gern JE, et al: Strategic plan for pediatric respiratory diseases research: An NHLBI working group report. Proc Am Thorac Soc 2009; 6: 1-10
179. Lands LC, Allen J, Cloutier M, et al; Pediatric Assembly of American Thoracic Society Subcommittee: ATS Consensus Statement: Research opportunities and challenges in pediatric pulmonology. Am J Respir Crit Care Med 2005; 172: 776-780
180. Thomas NJ, Shaffer ML, Willson DF, et al: Defining acute lung disease in children with the oxygenation saturation index. Pediatr Crit Care Med 2010; 11: 12-17
181. Horváth I, Hunt J, Barnes PJ, et al; ATS/ERS Task Force on Exhaled Breath Condensate: Exhaled breath condensate: Methodological recommendations and unresolved questions. Eur Respir J 2005; 26: 523-548
182. Randolph AG: Management of acute lung injury and acute respiratory distress syndrome in children. Crit Care Med 2009; 37: 2448-2454
183. Hopkins RO, Weaver LK, Collingridge D, et al: Two-year cognitive, emotional, and quality-of-life outcomes in acute respiratory distress syndrome. Am J Respir Crit Care Med 2005; 171: 340-347
184. Garland A, Dawson NV, Altmann I, et al; SUPPORT Investigators: Outcomes up to 5 years after severe, acute respiratory failure. Chest 2004; 126: 1897-1904
185. Carson SS, Cox CE, Holmes GM, et al: The changing epidemiology of mechanical ventilation: A population-based study. J Intensive Care Med 2006; 21: 173-182
186. Odetola FO, Clark SJ, Freed GL, et al: A national survey of pediatric critical care resources in the United States. Pediatrics 2005; 115: e382-e386
187. Randolph AG, Gonzales CA, Cortellini L, et al: Growth of pediatric intensive care units in the United States from 1995 to 2001. J Pediatr 2004; 144: 792-798
188. Briassoulis G, Filippou O, Natsi L, et al: Acute and chronic paediatric intensive care patients: Current trends and perspectives on resource utilization. QJM 2004; 97: 507-518